Brain Sciences
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2023
·Vol. 13
·期 2
·200
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IF 3.3
Li Wang,Zheng Gao,Gang Chen,Deqin Geng,Dianshuai Gao
Sleep disturbances are the most prevalent non-motor symptoms in the preclinical stage of Parkinson’s disease (PD). Adenosine, glial-derived neurotrophic factor (GDNF), and associated neurotransmitters are crucial in the control of sleep arousal. This study aimed to detect the serum levels of adenosine, GDNF, and associated neurotransmitters and explored their correlations with PD with sleep disorders. Demographic characteristics and clinical information of PD patients and healthy participants were assessed. Serum concentrations of adenosine, GDNF, and related neurotransmitters were detected by ELISA and LC-MS. The correlation between serum levels of adenosine, GDNF, and associated neurotransmitters and sleep disorders was explored using logistic regression. PD patients with sleep disorders had higher scores of HAMA, HAMD, ESS, UPDRS-III, and H-Y stage. Lower levels of adenosine, GDNF, and γ-GABA were observed in PD patients who had sleep problems. Logistic regression analysis showed adenosine and GDNF were protective factors for preventing sleep disorders. Adenosine combined with GDNF had a higher diagnostic efficiency in predicting PD with sleep disorders by ROC analysis. This study revealed low adenosine and GDNF levels may be risk factors for sleep disorders in PD. The decrease of serum adenosine and GDNF levels may contribute to the diagnosis of PD with sleep disturbances.Keywords:Parkinson’s disease;sleep disorders;adenosine;GDNF;neurotransmitters
研究领域:
神经科学
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医学
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DOI
PubMed
高影响因子
Acta Biomaterialia
·
2024
·
IF 9.4
Jiashang Liu,Ruijia Yan,Bixue Wang,Shu Chen,Hua Hong,Changsheng Liu,Xi Chen
Motor functional improvement represents a paramount treatment objective in the post-spinal cord injury (SCI) recovery process. However, neuronal cell death and axonal degeneration following SCI disrupt neural signaling, impeding the motor functional recovery. In this study, we developed a multifunctional decellularized spinal cord-derived extracellular matrix (dSECM), crosslinked with glial cell-derived neurotrophic factor (GDNF), to promote differentiation of stem cells into neural-like cells and facilitate axonogenesis and remyelination. After decellularization, the immunogenic cellular components were effectively removed in dSECM, while the crucial protein components were retained which supports stem cells proliferation and differentiation. Furthermore, sustained release of GDNF from the dSECM facilitated axonogenesis and remyelination by activating the PI3K/Akt and MEK/Erk pathways. Our findings demonstrate that the dSECM-GDNF platform promotes neurogenesis, axonogenesis, and remyelination to enhance neural signaling, thereby yielding promising therapeutic effects for motor functional improvement after SCI. Statement of significance The dSECM promotes the proliferation and differentiation of MSCs or NSCs by retaining proteins associated with positive regulation of neurogenesis and neuronal differentiation, while eliminating proteins related to negative regulation of neurogenesis. After crosslinking, GDNF can be gradually released from the platform, thereby promoting neural differentiation, axonogenesis, and remyelination to enhance neural signaling through activation of the PI3K/Akt and MEK/Erk pathways. In vivo experiments demonstrated that dSECM-GDNF/MSC@GelMA hydrogel exhibited the ability to facilitate neuronal regeneration at 4 weeks post-surgery, while promoting axonogenesis and remyelination at 8 weeks post-surgery, ultimately leading to enhanced motor functional recovery. This study elucidates the ability of neural regeneration strategy to promote motor functional recovery and provides a promising approach for designing multifunctional tissue for SCI treatment.
研究领域:
神经科学
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组织工程
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再生医学
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干细胞生物学
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DOI
PubMed
高影响因子
iMeta
·
2025
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IF 33.2
Cunzheng Zhang,Yuzhu Chen,Ruqiao Duan,Yiming Zhang,Haonan Zheng,Jindong Zhang,Tao Zhang,Jingxian Xu,Kailong Li,Fei Pei,Liping Duan
Maternal health, specifically changes in the gut microbiota, can profoundly impact offspring health; however, our understanding of how gut microbiota alterations during the preconception period influence the offspring remains limited. In this study, we investigated the impact and mechanisms of preconception maternal gut dysbiosis on the development of the enteric nervous system (ENS) in mice. We found that preconception maternal exposure to antibiotics led to the abnormal development of the ENS in offspring, increasing their susceptibility to water avoidance stress at the adult stage. Metagenomic, targeted metabolomic, and transcriptomic analyses revealed that preconception antibiotic exposure disrupted the expression of genes crucial for embryonic ENS development by altering maternal gut microbiota composition. Multi-omics analysis combined with Limosilactobacillus reuteri and propionate gestational supplementation demonstrated that the maternal gut microbiota and metabolites may influence embryonic ENS development via the GPR41–GDNF/RET/SOX10 signaling pathway. Our findings highlight the critical importance of maintaining a healthy maternal gut microbiota before conception to support normal ENS development in offspring. Graphical Preconception administration of antibiotics to female mice reduces the abundance of Limosilactobacillus reuteri in the maternal gut microbiota during pregnancy, subsequently affecting propionate levels. Decreased propionate levels downregulated the expression of Gdnf / Ret / Sox10 mediated by GPR41, leading to abnormal development of the enteric nervous system during the embryonic period. This dysplasia results in colonic dysmotility, impaired colonic epithelium, and increased susceptibility to water-avoidance stress in offspring. Highlights Preconception maternal antibiotic exposure results in the abnormal development of the enteric nervous system (ENS) and intestinal mucosa in mouse offspring, thereby increasing their susceptibility to water avoidance stress in adulthood. Preconception maternal antibiotic exposure alters the composition of the maternal gut microbiota, leading to abnormal embryonic ENS development via the modulation of gene expression. Multi-omics analysis and supplementation with Limosilactobacillus reuteri and propionate during pregnancy indicate that the maternal gut microbiota and metabolites affect embryonic ENS development through the GPR41–GDNF/RET/SOX10 signaling pathway.
研究领域:
微生物学
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发育生物学
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神经科学
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胃肠病学
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DOI
PubMed
高影响因子
JOURNAL OF CELLULAR PHYSIOLOGY
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2024
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IF 4.5
Hairui Tian,Xingju Wang,Xiaoxiao Li,Weixiang Song,Jiaqi Mi,Kang Zou
In the orchestrated environment of the testicular niche, the equilibrium between self-renewal and differentiation of spermatogonial stem cells (SSCs) is meticulously maintained, ensuring a stable stem cell reserve and robust spermatogenesis. Within this milieu, extracellular vesicles, specifically exosomes, have emerged as critical conveyors of intercellular communication. Despite their recognized significance, the implications of testicular exosomes in modulating SSC fate remain incompletely characterized. Given the fundamental support and regulatory influence of Sertoli cells (SCs) on SSCs, we were compelled to explore the role of SC-derived exosomes (SC-EXOs) in the SSC-testicular niche. Our investigation hinged on the hypothesis that SC-EXOs, secreted by SCs from the testes of 5-day-old mice—a developmental juncture marking the onset of SSC differentiation—participate in the regulation of this process. We discovered that exposure to SC-EXOs resulted in an upsurge of PLZF, MVH, and STRA8 expression in SSC cultures, concomitant with a diminution of ID4 and GFRA1 levels. Intriguingly, obstructing exosomal communication in a SC-SSC coculture system with the exosome inhibitor GW4869 attenuated SSC differentiation, suggesting that SC-EXOs may modulate this process via paracrine signaling. Further scrutiny revealed the presence of miR-493-5p within SC-EXOs, which suppresses Gdnf mRNA in SCs to indirectly restrain SSC differentiation through the modulation of GDNF expression—an indication of autocrine regulation. Collectively, our findings illuminate the complex regulatory schema by which SC-EXOs affect SSC differentiation, offering novel perspectives and laying the groundwork for future preclinical and clinical investigations.
研究领域:
生殖生物学
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干细胞生物学
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分子生物学
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DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
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2025
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IF 13.2
Ainizier Yalikun,Sulong Wang,Li Li,Kai Liu,Yimurang Hamiti,Aihemaitijiang Yusufu
Peripheral nerve injuries, which can lead to nerve transection or long-segment defects, remain a challenging medical issue. Combining nerve guidance conduits (NGCs) with the delivery of neurotrophic factors is a promising therapeutic approach for peripheral nerve defects. In this study, oriented porous nerve conduits were fabricated by electrospinning a poly(lactic- co -glycolic acid) (PLGA) sheath around a chitosan–collagen (CH–CO) core at a 1:1 mass ratio. Separately, GDNF-loaded composite microspheres (CP-MSs) composed of chitosan methacryloyl and PLGA were produced via microfluidic technology. The CH-CO (1:1)/PLGA conduits that were produced exhibited optimal porosity, degradation properties, and mechanical stability, demonstrating excellent biocompatibility with PC12 and RSC96 cells in vitro. The CP-MSs, optimized for size and dispersion at specific aqueous and oil flow rates, had a diameter of 73.2 ± 4.5 μm, with an encapsulation efficiency and drug loading of 81.2 ± 1.9% and 0.84 ± 0.11%, respectively. In vitro studies showed that CP-MSs were biocompatible and released GDNF sustainably, promoting PC12 cell differentiation and maintaining biological activity for 6 weeks. Histological and functional assessments of nerve regeneration confirmed that CP-MSs combined with the CH-CO (1:1)/PLGA conduits significantly enhanced peripheral nerve regeneration, as evidenced by axonal myelination, longitudinal axonal growth, and functional recovery. This study demonstrated the feasibility of CP-MSs with oriented multichannel CH-CO1:1/PLGA conduits for effective nerve defect repair, indicating its promising application in peripheral nerve regeneration.
研究领域:
生物医学工程
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组织工程
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药剂学
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神经科学
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产品关联
DOI
高影响因子
ENVIRONMENTAL TOXICOLOGY
·
2023
·Vol. 38
·期 11
·2595-2607
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IF 4.5
Jue Wang,Sai Gu,Bo Qin
Background Exosomes are applied as biomarkers in several diseases according to their disease-specific profiles. However, the exosomes effects in functional dyspepsia (FD) are still fragmentary. Here we examined the role of Eosinophil and mast cell derived-exosomes in FD progression. Methods Fifty FD subjects and age- and sex-matched healthy controls were included in this retrospective cohort study. Duodenal mucosa and gastric juice were collected to analyze molecular difference. Eosinophil and mast cell were evaluated by immunofluorescence and microarray was subjected to examine the expression levels of NEAT1, miR-211-5p, and glial cell line-derived neurotrophic factor (GDNF), which were subsequently were tested by quantitative reverse transcription PCR (RT-qPCR) validation cohorts. CCK-8 assays, and wound healing assays were used to evaluate integrity of intestinal mucosal barrier in vitro. Rats' weights and gastric emptying rates were used as evaluation of FD severity in vivo. Results Eosinophil and mast cell were enriched and secreted more exosomes in duodenal mucosa of FD patients. We identified differential lncRNAs that were consistently and significantly up regulated in FD cases. Of these, NEAT1 was further validated by RT-qPCR and had closely relationship with GDNF. MiR-211-5p level was found to be reduced in FD and negatively related with NEAT1 and GDNF. Furthermore, NEAT1and GDNF relived FD while miR-211-5p made symptoms worse. The NEAT1/miR-211-5p/GDNF axis had a good predictive ability for FD. Conclusions The NEAT1/miR-211-5p/GDNF could be a potential FD biomarker.
研究领域:
胃肠病学
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分子生物学
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病理生理学
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DOI
PubMed
高影响因子
American Journal of Translational Research
·
2021
·
IF 4.06
Shan Jiang,Chonghe Wang,Jingyao Zhu,Xuezhu Huang
Objective: To investigate the regulatory mechanism of sevoflurane-induced neuronal apoptosis through analyzing the expression of glial cell-derived neurotrophic factor (GDNF) mediated by miR-133, sponged by long non-coding RNA (lncRNA) CDKN2B-AS1. Methods: An in vitro cell injury model was established by using different concentrations of sevoflurane and primary hippocampal neurons. Cell proliferation was detected by Cell Counting Kit-8 (CCK-8); caspase-3 and caspase-9 activities were detected by colorimetry, and apoptotic cells were determined by Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Fluorescence in situ hybridization (FISH) analysis was used to detect localized expression of CDKN2B antisense RNA 1 (CDKN2B-AS1), and dual-luciferase reporter assay was employed to verify the correlation of CDKN2B-AS1 and miR-133, and of miR-133 and GDNF. The expression of CDKN2B-AS1, miR-133, and GDNF mRNA in the cell injury model were measured by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Western blot was utilized to detect the expression of GDNF protein in the cell injury model. Results: In the cell injury model, CDKN2B-AS1 was highly expressed in the cytoplasm, and CDKN2B-AS1 and GDNF were downregulated and miR-133 was upregulated as detected by qRT-PCR (all P<0.05). The connections between CDKN2B-AS1 and miR-133, and between miR-133 and GDNF were confirmed. That is, CDKN2B-AS1 regulated the expression of GDNF by adsorbing miR-133 (all P<0.05). In cells treated with sevoflurane, overexpression of CDKN2B-AS1 could inhibit caspase-3 and caspase-9 activities and the degree of apoptosis. miR-133 could partially alleviate the effect of overexpressing CDKN2B-AS1 on cells, and si-GDNF the effect of miR-133 inhibitor (all P<0.05). Conclusion: lncRNA CDKN2B-AS1 can up-regulate the expression of GDNF, inhibit neuronal apoptosis, and ease the toxic effect of sevoflurane on neural cells by acting as a sponge to adsorb miR-133.
研究领域:
神经科学
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分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
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